HMPV/hPIV3 mRNA vaccine composition
Provided herein are vaccine composition comprising a chemically-modified messenger ribonucleic acid (mRNA) encoding a hMPV fusion (F) glycoprotein and a chemically-modified mRNA encoding a hPIV3 F glycoprotein formulated in a cationic lipid nanoparticle formulation, and related method for inducing an antigen-specific immune response.
1. A method of inducing in a human subject human metapneumovirus (hMPV) and human parainfluenza virus 3 (hPIV3) neutralizing antibody titers, the method comprising administering to the human subject a vaccine composition comprising:
(a) an mRNA comprising a nucleic acid sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 1; and
(b) an mRNA comprising a nucleic acid sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 2, wherein the mRNA of (a) and the mRNA of (b) are in a lipid nanoparticle (LNP).
2. The method of claim 1 , wherein the vaccine composition comprises a 25 μg to 150 μg dose of mRNA.
3. The method of claim 2 , wherein the vaccine composition comprises a 150 μg dose of mRNA.
4. The method of claim 1 , wherein the vaccine composition comprises a 25 μg to 75 μg dose of mRNA.
5. The method of claim 4 , wherein the vaccine composition comprises a 75 μg dose of mRNA.
6. The method of claim 4 , wherein the vaccine composition comprises a 25 μg dose of mRNA.
7. The method of claim 1 , wherein the lipid nanoparticle comprises 45-55 mole percent (mol %) ionizable cationic lipid, 5-15 mol % non-cationic lipid, 35-40 mol % sterol, and 1-2 mol % PEG-modified lipid.
8. The method of claim 7 , wherein the lipid nanoparticle comprises 50 mol % Compound I ionizable cationic lipid, 10 mol % DSPC (1,2-Distearoyl-sn-glycero-3-phosphocholine), 38.5 mol % cholesterol, and 1.5 mol % DMG-PEG (1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000), wherein Compound I has the formula:
9. The method of claim 1 , wherein the nucleotide sequence of the mRNA of (a) encodes an hMPV F glycoprotein comprising the amino acid sequence of SEQ ID NO: 8.
10. The method of claim 1 , wherein the nucleotide sequence of the mRNA of (b) encodes an hPIV3 F glycoprotein comprising the amino acid sequence of SEQ ID NO: 10.
11. The method of claim 1 , wherein the mRNA of (a) comprises an open reading frame sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 7 and encodes an hMPV glycoprotein F.
12. The method of claim 11 , wherein the mRNA of (a) comprises an open reading frame sequence that comprises the nucleic acid sequence of SEQ ID NO: 7 and encodes an hMPV glycoprotein F.
13. The method of claim 1 , wherein the mRNA of (b) comprises an open reading frame sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 9 and encodes an hPIV3 glycoprotein F.
14. The method of claim 13 , wherein the mRNA encoding the hPIV3 glycoprotein comprises an open reading frame sequence that comprises the nucleic acid sequence of SEQ ID NO: 9 and encodes an hPIV3 glycoprotein F.
15. The method of claim 1 , wherein the mRNA of (a) comprises the nucleic acid sequence of SEQ ID NO: 1.
16. The method of claim 1 , wherein the mRNA of (b) comprises the nucleic acid sequence of SEQ ID NO: 2.
17. A method of inducing in a human subject human metapneumovirus (hMPV) and human parainfluenza virus 3 (hPIV3) neutralizing antibody titers, the method comprising administering to the human subject a vaccine composition comprising a 25 μg to 150 μg dose of messenger ribonucleic acid (mRNA) formulated in a lipid nanoparticle (LNP), wherein the mRNA comprises mRNA encoding an hMPV fusion (F) glycoprotein comprising the amino acid sequence of SEQ ID NO: 8 and mRNA encoding an hPIV3 F glycoprotein comprising the amino acid sequence of SEQ ID NO: 10,
wherein the lipid nanoparticle comprises 45-55 mole percent (mol %) Compound I ionizable cationic lipid, 5-15 mol % DSPC, 35-40 mol % cholesterol, and 1-2 mol % DMG-PEG, and the geometric mean titer (GMT) of hMPV neutralizing antibodies and hPIV3 neutralizing antibodies induced in the subject is increased by at least 3-fold within 30 days of administering the vaccine composition, relative to baseline, and wherein Compound I has the formula:
18. The method of claim 17 , wherein the mRNA encoding the hMPV glycoprotein comprises an open reading frame sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 7, and the mRNA encoding the hPIV3 glycoprotein comprises an open reading frame sequence having at least 95% identity to the nucleic acid sequence of SEQ ID NO: 9.